The H2 histamine receptor is also coupled to the Gαs protein. Release of histamine from mast cells is primarily responsible for immediate hypersensitivity reaction in the skin. Clinical observations of our patients with MAS suggest increased responsiveness to histamine. We speculate that this results from upregulation of Gαs coupled to H2 receptor. In our identified patients, this has been manifested as asthma, chronic hives, dermatographism, contact hypersensitivities, drug reactions, ulcers, as well as anaphylactic reactions to seafood, dyes, and latex. Approximately 75% of our patients with MAS exhibit one or more of the aforementioned reactions. Anaphylaxis has occurred in three separate patients.